Omega-3 enriched fish oil-in-water parenteral nutrition emulsions

ABSTRACT

An emulsion is provided including: an oil component and a water component, the oil component including: fish oil triglycerides in an amount of about 60% to about 90% based on the weight of the oil component; wherein the fish oil triglycerides include omega-3 fatty acids, expressed as triglycerides, in an amount of at least 60%, based on the total weight of the fatty acids of the fish oil triglycerides; wherein the fish oil triglycerides include a total amount of EPA and DHA, expressed as triglycerides, of at least 45%, based on the total weight of the fatty acids of the fish oil triglycerides; and, at least one medium-chain triglyceride, wherein a total amount of the at least one medium-chain triglyceride is from about 10% to about 40% based on the weight of the oil component.

CROSS-REFERENCE TO RELATED APPLICATION

This application is a 35 USC §371 national stage application ofInternational Application No. PCT/US2010/000723 filed on Mar. 11, 2010,which is a continuation-in-part of U.S. application Ser. No. 12/382,196filed on Mar. 11, 2009, wherein the entire contents of each of the aboveapplications are incorporated herein by reference.

BACKGROUND

1. Field

The present disclosure relates to an emulsion and a compositioncontaining at least omega-3 acid triglycerides and a medium-chaintriglyceride. The emulsion can be an oil-in-water emulsion. The emulsionand composition can be used, for example, in parenteral administration.

2. Related Art

Oil-in-water parenteral emulsions have been used clinically fornutritional and medical purposes. Of the various types of oils used,historically soybean oil was first introduced almost 50 years ago andthus has the greatest clinical experience.

Parenteral emulsions are described in International Publication No. WO97/19683, U.S. Pat. No. 5,874,470 and U.S. Patent ApplicationPublication No. 2004/0247693.

U.S. Patent Application Publication No. 2004/0247693 discloses anisotonic lipid emulsion including (i) about 60 to about 95% by weight ofmedium chain triglycerides, and (ii) about 5 to 40% by weight of fishoil, based on the total amount of lipids in the emulsion, under theproviso that the emulsion does not contain vegetable oils.

SUMMARY

According to an exemplary aspect, an emulsion is provided comprising:

an oil component and a water component, the oil component comprising:

-   -   fish oil triglycerides in an amount of about 60% to about 90%        based on the weight of the oil component;        -   wherein the fish oil triglycerides comprise omega-3 fatty            acids, expressed as triglycerides, in an amount of at least            60%, based on the total weight of the fatty acids of the            fish oil triglycerides;        -   wherein the fish oil triglycerides comprise a total amount            of EPA and DHA, expressed as triglycerides, of at least 45%,            based on the total weight of the fatty acids of the fish oil            triglycerides; and,    -   at least one medium-chain triglyceride oil, wherein a total        amount of the at least one medium-chain triglyceride oil is from        about 10% to about 40% based on the weight of the oil component.

According to another exemplary aspect, an oil composition suitable foruse as an oil component of an oil-in-water emulsion is provided,comprising:

fish oil triglycerides in an amount of about 60% to about 90% based onthe weight of the composition;

-   -   wherein the fish oil triglycerides comprise omega-3 fatty acids,        expressed as triglycerides, in an amount of at least 60% based        on the total weight of the fatty acids of the fish oil        triglycerides;    -   wherein the fish oil triglycerides comprise a total amount of        EPA and DHA, expressed as triglycerides, of at least 45%, based        on the total weight of the fatty acids of the fish oil        triglycerides; and,

at least one medium-chain triglyceride oil, wherein a total amount ofthe at least one medium-chain triglyceride oil is from about 10% toabout 40% based on the weight of the composition.

According to another exemplary aspect, an emulsion is providedcomprising:

an oil component and a water component, the oil component comprising:

-   -   fish oil triglycerides in an amount of greater than 50% to about        90% based on the weight of the oil component of the emulsion;        -   wherein the fish oil triglycerides comprise omega-3 fatty            acids, expressed as triglycerides, in an amount of at least            60%, based on the total weight of the fatty acids of the            fish oil triglycerides;        -   wherein the fish oil triglycerides comprise a total amount            of EPA and DHA. expressed as triglycerides, of at least 45%,            based on the total weight of the fatty acids of the fish oil            triglycerides; and, a medium-chain triglyceride oil.

According to another exemplary aspect, an emulsion is providedcomprising:

an oil component and a water component, the oil component comprising:

-   -   fish oil triglycerides in an amount of about 31% to about 90%        based on the weight of the oil component of the emulsion;        -   wherein the fish oil triglycerides comprise omega-3 fatty            acids, expressed as triglycerides, in an amount of at least            60%, based on the total weight of the fatty acids of the            fish oil triglycerides;        -   wherein the fish oil triglycerides comprise a total amount            of EPA and DHA, expressed as triglycerides, of at least 45%,            based on the total weight of the fatty acids of the fish oil            triglycerides; and, a medium-chain triglyceride;    -   wherein the emulsion is an oil-in-water emulsion, and wherein        the concentration of the oil component in the emulsion is 5        g/100 mL to less than 20 g/100 mL, or the concentration of the        oil component in the emulsion is greater than 20 g/100 mL to 30        g/100 mL.

According to another exemplary aspect, an emulsion is providedcomprising:

an oil component and a water component, the oil component comprising:

-   -   fish oil triglycerides present in an amount of about 31% to        about 90% based on the weight of the oil component of the        emulsion;        -   wherein the fish oil triglycerides comprise omega-3 fatty            acids, expressed as triglycerides, in an amount of at least            60%, based on the total weight of the fatty acids of the            fish oil triglycerides;        -   wherein the fish oil triglycerides comprise a total amount            of EPA and DHA, expressed as triglycerides, of at least 45%,            based on the total weight of the fatty acids of the fish oil            triglycerides;    -   a medium-chain triglyceride oil; and    -   a vegetable oil.

According to another exemplary aspect, an emulsion is providedcomprising:

an oil component and a water component, the oil component comprising:

-   -   fish oil triglycerides present in an amount of about 31% to        about 90% based on the weight of the oil component of the        emulsion;        -   wherein the fish oil triglycerides comprise omega-3 fatty            acids, expressed as triglycerides, in an amount of at least            60%, based on the total weight of the fatty acids of the            fish oil triglycerides;        -   wherein the fish oil triglycerides comprise a total amount            of EPA and DHA, expressed as triglycerides, of at least 45%,            based on the total weight of the fatty acids of the fish oil            triglycerides; and,    -   a medium-chain triglyceride;

wherein the emulsion is an oil-in-water emulsion, and wherein theconcentration of the oil component in the emulsion is 5 g/100 mL to 17.5g/100 mL, or the concentration of the oil component in the emulsion is22.5 g/100 mL to 30 g/100 mL.

According to another exemplary aspect, an oil-in-water emulsion isprovided comprising:

a) fish oil triglycerides consisting of glycerol which is esterifiedwith fatty acids wherein said fatty acids comprise EPA and DHA in anamount of at least 45% by weight of said fatty acids and the totalamount of omega-3 fatty acids is at least 60% by weight of said fattyacids, and

b) at least one medium chain triglyceride oil, and

wherein the fish oil triglycerides are present in an amount of at least51% by weight based on the total weight of the oil component, and themedium chain triglycerides are present in an amount of 10 to 49% byweight based on the total weight of the oil component.

According to another exemplary aspect, the fish oil triglycerides arepresent in an amount ranging from 51 to 90% by weight based on the totalweight of the oil component.

According to another exemplary aspect, the oil component additionallycomprises a vegetable oil.

According to another exemplary aspect, the vegetable oil is present inan amount of up to 10 percent by weight, preferably from 2 to 8% byweight based on the total weight of the oil component of theoil-in-water emulsion.

According to another exemplary aspect, the vegetable oil is selectedfrom the group consisting of soybean oil and safflower oil and mixturesthereof.

According to another exemplary aspect, the oil-in-water emulsioncomprises the oil component in an amount ranging from 5 to 30 g/100 mL,preferably 15 to 25 g/100 mL, for example, 20 g/100 mL of the emulsion.

According to another exemplary aspect, the oil-in-water emulsionadditionally comprises at least one phospholipid emulsifier componentwhich is preferably selected from the group of phospholipids derivedfrom egg or soya.

According to another exemplary aspect, the phospholipid emulsifiercomponent is a phosphatidyl choline.

According to another exemplary aspect, the phospholipid emulsifiercomponent is present in a weight ratio of phospholipid to triglyceridesranging from 0.05 to 0.07, preferably 0.06.

According to another exemplary aspect, the oil-in-water emulsionadditionally comprises an isotonic agent, preferably in a concentrationranging from 20 to 25 g/L.

According to another exemplary aspect, the oil-in-water emulsioncomprises glycerol as isotonic agent.

According to another exemplary aspect, the oil-in-water emulsioncomprises a pH-adjusting agent.

According to another exemplary aspect, the oil-in-water emulsioncomprises sodium oleate as the pH adjusting agent.

According to another exemplary aspect, the pH adjusting agent is presentin a concentration of up to 3 g/L.

According to another exemplary aspect, the pH value of the emulsionranges from 6 to 9, preferably from 6 to 8.5, more preferably from 7.5to 8.5.

According to another exemplary aspect, the oil-in-water emulsionadditionally comprises an antioxidant which is preferably present in aconcentration of up to 1 g/L.

According to another exemplary aspect, the antioxidant is α-tocopherol.According to another exemplary aspect, the emulsion is parenterallyapplicable.

According to another exemplary aspect, the mean droplet diameter of theoil droplets is below 250 nm, preferably below 240 nm at 20° C.

According to another exemplary aspect, a pharmaceutical composition isprovided comprising or consisting of an oil-in-water emulsion.

According to another exemplary aspect, a pharmaceutical composition isprovided for use in the prophylaxis or treatment of the group ofdiseases consisting of systemic inflammatory response syndrome (SIRS),respiratory distress syndrome (RDS), nutritional and/or dietary cause ofliver disease, an iatrogenic cause of liver disease, a pathologicalcause of liver disease, an immune modulation, head trauma, postoperative surgical stress, a myocardial infarction and cystic fibrosis.

According to another exemplary aspect, a composition is provided thatincludes an enriched fish oil according to Pharm Eur 1352 specificationswhich is a “processed oil” that is fortified to contain a higherproportion of the bioactive omega-3 fatty acids compared to naturalsources.

According to another exemplary aspect, a composition is provided thatincludes an omega-3 essential fatty acid (EFA), and an omega-6 EFA of afish oil, wherein the omega-6 EFA is present in an amount that minimizesa negative clinical impact from excessive intakes of thepro-inflammatory fatty acid mediators.

According to another exemplary aspect, an emulsion is provided in whicha final o/w emulsion concentration is from about 5 g/100 mL to about 30g/100 mL, for example, a concentration of about 20 g/100 mL.

According to another exemplary aspect, a composition is provided thatincludes medium-chain fatty acids (FAs) of a medium-chain triglyceride(MCT) oil, wherein the medium-chain FAs are present in amounts effectiveto facilitate the metabolic clearance of fish oil. For example, the MCTscan be present in an amount that is effective to facilitate themetabolic clearance of long-chain triglycerides.

According to another exemplary aspect, the MCTs can function as asuitable energy source that is at least equal or comparable in itsnitrogen-sparing properties to long chain triglycerides, but withoutmetabolic consequence to inflammatory processes in patients.

According to another exemplary aspect, a composition is provided thatincludes MCTs in amounts effective to maintain the stability of theemulsion.

According to another exemplary aspect, there is a reduction of theconcentration of saturated long-chain fatty acids (LCFAs) in the oilsource of the emulsion which can result in a reduction of adverseclinical effects such as inflammation, glucose intolerance and/orinsulin resistance.

According to another exemplary aspect, the composition of the oil phaseof the emulsion can be adjusted to optimize the response to intravenousnutritional support.

According to another exemplary aspect, a composition of the oil phase ofthe emulsion is provided that can include n3-FAs in an amount that iseffective to exert a desirable pharmacological effect, for example, tocombat deleterious inflammatory responses or preserve vital organfunctions.

According to another exemplary aspect, a composition is provided thatcan include an optimal balance of triglycerides in order to reduce oreliminate the toxicity that can result from the parenteraladministration of conventional o/w emulsions.

DETAILED DESCRIPTION

An exemplary embodiment is directed to a novel parenteral lipid emulsioncomposition comprising: a relatively high concentration of an oilderived from fish oil triglycerides, that is highly enriched inlong-chain omega-3 (n-3) fatty acids (n3-FAs); a relatively lowconcentration of medium-chain fatty acids from medium chaintriglycerides (MCTs); and optionally an amount of long-chain omega-6(n-6) fatty acids (n6-FAs).

As used herein, the terms “fish oil” and “fish oils” pertain toconstituents such as triglycerides which are present in a fish oil, andconstituents such as triglycerides which are derivatives or productsobtained from a fish oil. In an exemplary embodiment, fish oiltriglycerides described herein include triglycerides derived orsynthesized from a fish oil. For example, the fish oil triglycerides caninclude a synthetically derived oil containing re-esterified omega-3fatty acids, which have been derived from a fish oil. For example, thesynthetically derived oil can be derived from a fish oil in accordancewith an enrichment process that is effective to separate desirable fattyacids (such as omega-3 fatty acids, for example, EPA and DHA) from, forexample, certain undesirable fatty acids (for example, saturatedlong-chain FAs). An example of such enrichment process is separation bymolecular distillation and/or filtration. In an exemplary embodiment,the synthetically derived oil can be derived in a manner that isconsistent with EP 1352, discussed below.

The oil that is derived from fish oil can contain n3-FAs at aconcentration higher than that occurring in natural sources. Themedium-chain fatty acids from medium chain triglycerides (MCTs) can besaturated medium-chain fatty acids. The n6-FAs can be provided from avegetable oil, for example, in order to meet EFA requirements. In oneembodiment, the composition of such as an emulsion can be stable, hasnormal metabolic clearance, and/or is well-tolerated by patients. Forexample, the emulsion can be an oil-in-water (o/w) emulsion.

An exemplary oil is derived from fish, and can be rich in thepolyunsaturated and bioactive omega-3 fatty acids. The oil component ofthe emulsion can contain fish oil triglycerides, for example, rich inomega-3 acid triglycerides. The fish oil triglycerides, can be presentfrom about 31% to about 90%, or from about 41% to about 90%, or fromabout 45% to about 90%, or from greater than 50% to about 90%, or fromabout 51% to about 90%, or from about 55% to about 90%, or from about60% to about 90%, or from about 61% to about 90%, or from about 70% toabout 90%, or from about 71% to about 90%, or from about 80% to about90%, or from about 40% to about 80%, or from about 50% to about 70%, orfrom about 60% to about 65%, based on the total weight of the oilcomponent of the emulsion. For example, by employing exemplary ranges offish oil triglycerides, the amount of esterified omega-3 fatty acidsdelivered to a human body can be increased. For example, Applicant hasrecognized the clinical significance of the absolute intake of omega-3fatty acids, and that such absolute intake of omega-3 fatty acids can beincreased by employing, for example, the exemplary ranges of fish oiltriglycerides. For example, Applicants have recognized that in at leastsome applications, for example cardiovascular health indications, theabsolute intake of omega-3 fatty acids can be a more accurate indicatorof overall efficacy than the ratio of omega-3 fatty acids to omega-6fatty acids. See, for example, Stanley et al, 2007.

The fish oil triglycerides can be 20- to 22-carbon compounds and cancontain 3 or more double bonds located at the 3^(rd) position from themethyl end of the long-chain fatty acid (LCFA) molecule. Standardnotation for the various fatty acids (FAs) includes: 1) carbon number,followed by, 2) the number of double bonds, and ending with 3) theposition of the double bond relative to the methyl position (or “n3” inthe case of the LCFA from fish oil). In particular, the marine oil canbe highly enriched with two major n3-FAs, i.e., eicosapentaenoic acid,or EPA (20:5n3), and docosahexaenoic acid, or DHA (22:5n3). The marineoil can contain lesser amounts of other n3-FAs, such as docosapentaenoicacid, or DPA (22:6n3). The fish oil component of the o/w parenterallipid emulsion can represent oils from a mixture of fatty fish families,such as from the following species: Engraulidae (e.g., anchovies),Carangidae (e.g., mackerel), Clupeidae (e.g., herring), Osmeridae (e.g.,smelt), Salmonidae (e.g., salmon) and Scombridge (tuna).

In the European Pharmacopeia (EP), there are two monographs (i.e., EP1352 entitled “Omega-3 Acid Triglycerides”, and, EP 1912 entitled “FishOil, Rich in Omega-3 Acids”) that pertain to fish oil (EP 1352, EP 1912,2008). The monograph EP 1352 substantially differs from EP 1912 in thatthe composition and requirements for the bioactive n3-FAs in EP 1352 aremuch higher than in EP 1912 (EP 1352: EPA+DHA≧45%; total n3-FAs≧60% vs.EP 1912: EPA:≧13%; DHA≧9%; total n3-FAs≧28%). The levels of n3-FAs in EP1912 are consistent with those found in nature. By comparison, in EP1352, the n3-FA concentrations are substantially higher and can beobtained by an enrichment process such as molecular distillation,whereby certain undesirable LCFAs that are present, for example,myristic acid, palmitic acid and stearic acid, are removed. In so doing,the concentrations of all FAs present, and particularly the n3-FAs, areproportionately elevated (Driscoll, 2008a).

In an exemplary embodiment, the fish oil triglycerides can includeomega-3 fatty acids, expressed as triglycerides, in an amount of atleast 60%, based on the total weight of the fatty acids of the fish oiltriglycerides. In an exemplary embodiment, the fish oil triglyceridescan include a total amount of EPA and DHA, expressed as triglycerides,of at least 45%, based on the total weight of the fatty acids of thefish oil triglycerides. For example, a fatty acid that is expressed as atriglyceride can be referred to as an esterified fatty acid. Forexample, the fatty acids and omega-3 fatty acids (such as, for example,EPA and DHA) discussed herein refer to the constituent parts of suchacids in a fish oil triglyceride, in accordance with EP 1352. Forexample, the fatty acids and omega-3 fatty acids (such as, for example,EPA and DHA) discussed above can be in their esterified form whenpresent in the fish oil triglycerides.

The fish oil triglycerides can contain at least one n6-FA, for example,a plurality of n6-FAs. The at least one n6-FA can include, for example,arachidonic acid or AA, (20:4n6) and linoleic acid or LA, (18:2n6).Additionally or alternatively, the n3-FA, alpha linolenic acid or ALA,(18:3n3) can be present. For example, the total content of the at leastone n6-FA can be from about 0.1% to about 1.0%, or from about 0.2% toabout 0.9%, or from about 0.3% to about 0.8%, or from about 0.4% toabout 0.7%, or from about 0.5% to about 0.6%, based on the weight of theoil component of the emulsion.

An exemplary second component of the oil component of the emulsion caninclude at least one medium chain triglyceride (MCT) oil, for example,at a plurality of exemplary MCT concentrations. For example, the atleast one MCT oil can be present from about 10% to about 69%, or fromabout 10% to about 40%, or from about 10% to about 30%, or from about10% to about 20%, or from about 10% to about 15%, or from about 20% toabout 60%, or from about 30% to about 50%, or from about 40% to about45%, based on the total weight of the oil component of the emulsion. Forexample, by employing exemplary ranges of MCT concentrations, the amountof esterified omega-3 fatty acids delivered to a human body can beincreased. For example, by employing exemplary MCT concentrations, theamount of esterified omega-3 fatty acids delivered to a human body canbe increased with usage of a relatively smaller amount of MCTs, whilestill achieving beneficial metabolic clearance and physicochemicalstability characteristics of the emulsion.

For example, the at least one MCT oil can include saturated medium chainfatty acids, for example, a plurality of saturated medium chain fattyacids. In an exemplary embodiment, the MCTs include a mixture of fattyacids having from 6 to 12 carbon atoms. The MCT oil can be derived froma plant such as a fruit or vegetable, for example, a plurality ofplants. The MCT oil can contain caprylic acid (for example, in an amountof about 50% to about 80% by weight of the MCT oil), an 8-carbonsaturated FA (8:0). The MCT oil can contain capric acid (for example, inan amount of about 20% to about 50% by weight of the MCT oil), a10-carbon saturated FA (10:0). For example, the medium-chaintriglycerides can contain caprylic acid and capric acid, in an amount ofat least 90% by weight of the MCT oil. The description of the MCT oilfor use in this disclosure can, for example, meet the requirements of EPmonograph 0868, entitled “Triglycerides, Medium Chain” (Triglyceridasaturate media) (EP 0868, 2008).

The oil component can optionally include a vegetable oil. The vegetableoil can include, for example, soybean oil, safflower oil or acombination thereof. The vegetable oil can, for example, be rich in then6-FA, LA, and/or can contain lesser amounts of the n3-FA, ALA.

The emulsion can optionally include at least one additional ingredient,a pharmaceutical adjuvant. The at least one additional ingredient caninclude, for example, egg phospholipid, sodium oleate, glycerol,alpha-tocopherol and sodium hydroxide and/or sterile water. Suchingredients can be used, for example, to stabilize the emulsion and makesuitable its use for intravenous administration in accordance withpharmacopeial specifications.

Oil-in-water parenteral emulsions can be used clinically for nutritionaland medical purposes. Of the various types of oils used, historicallysoybean oil was first successfully introduced in the clinical settingalmost 50 years ago and thus has generated the greatest clinicalexperience, but more recent formulations have included other oils, suchas MCT, fish and olive oils. As a nutritional supplement, o/w parenteralemulsions are intended for use in patients having a dysfunctionalgastrointestinal tract, originating from, for example, mesentery arterythrombosis, requiring a massive small bowel resection that produces acondition known as “short bowel syndrome”. Consequently, such patientshave insufficient intestine and therefore are incapable of absorbingsufficient macronutrients (protein, carbohydrate and fat) andmicronutrients (electrolytes, vitamins and minerals). There are otherclinical indications for intravenous nutrition (e.g., radiationenteritis, bowel obstruction, high output ileostomies, etc.) that mayalso require life-long intravenous nutrition. In other clinical cases,intravenous nutrition is used as a temporary therapeutic maneuver, forexample, in critically ill patients to support the body's metabolicresponse to injury and infection. In the absence of oral intake, thesecatabolic conditions can produce large daily losses of vital bodyprotein and profound energy deficits. If prolonged or accompanied bypre-existing malnutrition, the absence of nutritional intervention mayincrease the risk of significant clinical morbidity or mortality(Driscoll, 2008b).

In the case of o/w parenteral emulsions containing fish oil, theseemulsions can provide the essential fatty acids (EFAs) from both the n-3FA, EPA, DHA and the n-6 FA, AA, which cannot be synthesized by thebody. In the case of parenteral o/w emulsions containing soybean oil,these emulsions can provide the precursors to these EFAs in the form ofALA for n3-FAs and LA for n6-FAs. Again, historically, the introductionof soybean oil was based on providing sufficient concentrations of ALA(7 to 11%) and very high amounts of LA (50 to 55%) to prevent EFAdeficiency. To meet the EFA requirements with soybean oil-basedparenteral emulsions, between 1 and 4% of daily minimum calories arerequired (Bistrian, 2003). Thus, for example, in a 2000 kcal adult diet,1% of caloric intake (as LA or ˜50% of soybean oil) would translate toapproximately 40 kcals, or a minimum of about 3.5 g of soybean oil perday (equal to 17.5 mLs of a 20% lipid emulsion); for a 100 kcal neonatediet, 1% of caloric intake would translate to 2 kcal (about 0.2 g perday, or 1 mL of the soybean oil emulsion) in order to meet EFArequirements.

In addition to being a source of EFAs, parenteral lipid emulsions canalso be prescribed as a daily source of energy or calories, often insubstitution of a portion of the calories that would be provided ascarbohydrate (hydrated dextrose or glucose), administered intravenously.The practice of prescribing both glucose and lipids as energy sources(or a “mixed-fuel system”) can be done to avoid significant metaboliccomplications associated with high doses of intravenous glucose. Theseinclude hyperglycemia and increased infectious risks, hepatic damagefrom the metabolic conversion of glucose to fat in the liver, increasedrespiratory dysfunction from excessive carbon dioxide productionassociated with hepatic lipogenesis in patients with impaired lungfunction, and other adverse effects. As a daily source of calories, fatintake from parenteral lipid emulsions is commonly prescribed in amountsranging between 20 and 40% of total caloric intake. Thus, for example,in a 2000 kcal adult diet, this represents 400 to 800 kcals, orapproximately 44 to 88 g per day, which is equal to about 220 to 440 mLsper day of a 20% oil-in-water emulsion. For a neonatal diet of 100 kcalsper day, this would equate to 20 to 40 kcals, or approximately 2.2 to4.4 g per day, equal to about 10 to 20 mLs per day of the same 20% lipidemulsion.

Although a soybean oil-based parenteral emulsion was the first safeintravenous o/w dispersion introduced in 1961, and therefore theformulation most widely used worldwide, soybean oil is not the optimallipid to use in the clinical setting. As a long-chain triglyceride (LCT)of plant origin, the most abundant “omega” fatty acid found in this oilis the polyunsaturated, essential (precursor) n6-FA, LA (50-55%),followed by the monounsaturated, non-essential n9-FA, oleic acid(18:1n9) (24-26%), followed by the polyunsaturated essential (precursor)n3-FA, ALA (7 to 11%). Due to the dominant presence of the n6-FA, LA,and considering both its pro-inflammatory role and the fact that it is aprecursor to the highly vasoactive “2-series” eicosanoids involvingprostagladins and thromboxanes, as well as the potent immunomodulatory“4-series” leukotrienes, soybean oil may adversely accentuate thesystemic inflammatory response and/or exacerbate the deterioration ofcertain functions of vital organs. During critical illness accompaniedby systemic inflammatory response syndrome (SIRS), for example, the“2-series” eicosanoids produced from the infusion of soybean oil-basedparenteral emulsions may worsen lung function in patients withrespiratory distress syndrome. In adults, for example, infusions ofsoybean oil-based lipid emulsions have produced two different adverseeffects on the lungs, which have been shown to be infusionrate-dependent (Mathru et al, 1991). In one case, infusions of 100 g ofa 20% soybean oil-based parenteral emulsion (i.e., 500 mL) over 10 hourswas associated with significantly increased shunt fraction frompre-infusion levels presumably via prostaglandin-mediated pulmonaryvasodilatation. This action is counter to the normal physiologicresponse when blood flow proportionately decreases to poorly ventilatedsegments of the lung during respiratory distress, known as hypoxicpulmonary vasoconstriction. This results in an unphysiologic mismatchbetween the normally balanced ventilation and perfusion in the lungs,where the body now makes futile attempts to perfuse poorly ventilatedareas of the lung. In contrast, the same infusion, but now infused overonly 5 hours, has been shown to produce the opposite effect, i.e.,vasoconstriction, evidenced by significant increases in mean pulmonaryartery pressure, which can also aggravate respiratory function byaugmenting the hypoxic pulmonary vasoconstrictive response topotentially pathological proportions (e.g., pulmonary hypertension).Similar adverse pulmonary responses have been associated with theinfusion of parenteral lipid emulsions rich in n6-FAs in infants(Prasertsom et al, 1996).

Another clinical example demonstrating the potential deleterious effectsassociated with the administration of conventional soybean oil-basedparenteral emulsions, rich in the pro-inflammatory n6-FAs, involveshepatotoxicity. For example, in acutely ill infants with SIRS, prolongedinfusion of soybean oil-based parenteral emulsions may induce apathological condition known as parenteral nutrition-associated liverdisease or PNALD. The PNALD condition often occurs with long-term use ofparenteral nutrition in infants and may lead to liver failure and theneed for liver transplantation. Clinical findings associated with PNALDinclude abnormal elevations of blood components observed in liverfunction tests, such as serum transaminases, bilirubin and alkalinephosphatase, due to hepatic fat accumulation, leading ultimately toorgan failure (Gura et al, 2006). The mechanism of liver injury is notcompletely understood but has been suggested to occur by a “two-hit”theory. The first “hit” occurs during the accumulation of fat in theliver, or hepatic steatosis. The second “hit” that follows occurs in aseries of subsequent steps beginning with inflammation and cellulardegeneration, followed by production of reactive oxygen species orperoxidation products causing oxidative stress, that ultimately causesdamage of liver tissue (Paquot et al, 2005). In infants developingPNALD, mortality approaches 100% within one year of the diagnosis (Waleset al., 2005). Adverse effects to the liver from chronic exposure tosoybean oil parenteral emulsions have been linked to adults requiringlong-term parenteral nutrition (Ling et al, 2001).

Clearly, therefore, in an exemplary embodiment, parenteral lipidemulsions containing high amounts of triglycerides rich in n6-FAs arenot optimal, and are associated with significant adverse events inpatients requiring intravenous nutrition. Therefore, development ofalternative lipid sources that decrease the concentration of n-6 FAs andtheir accompanying pro-inflammatory effects may be of great clinicalbenefit. The use of n9-FAs found in olive oil, such as themonounsaturated fatty acids that are less pro-inflammatory, may be ofsignificant benefit. The use of n3-FAs, however, such as thepolyunsaturated fatty acids producing the “3-series” eicosanoids, may beof the greatest clinical benefit. In fact, the latter n3-FAs from theimportant omega families of fatty acids that have shown great promiseand are the least pro-inflammatory, have also been shown to possessfavorable effects on vital organs, and produce importantimmunomodulatory effects (Wanten, 2007). Thus, the ideal parenterallipid emulsion would be one that is stable, provides a sufficient supplyof the EFAs, provides a dense source of energy or calories, minimizesthe adverse effects from pro-inflammatory FAs, improves functions ofvital organs, and possesses therapeutically beneficial immunomodulatoryeffects, particularly during acute illness.

Exemplary embodiments disclosed herein employ a new composition ofmatter containing oils, for example, from MCTs and LCTs, with noveldoses of the various saturated medium-chain fatty acids (for example, 8-to 10-carbon MCFAs) and, mainly unsaturated long-chain fatty acids (forexample, 18- to 22-carbon LCFAs) from the biologically important,essential FAs from n3 and n6 families. In the final oil composition ofthe parenteral o/w lipid emulsion, the resulting oil phase can be madeas a simple “physical” mixture or blend of the desired oils.Alternatively, specifically customized mixtures of “structured”triglycerides can be made via hydrolysis of FAs from the glycerolbackbones of different oils, followed by random transesterificationproducing both preferred as well as analog triglyceride combinations.Or, the “structured” triglycerides can be made via enzymatic synthesisby selected lipases that are region-specific, e.g., sn-1 and sn-3positions, and FA-specific, producing a purer form of chemically definedstructured triglycerides. No matter how they are prepared, the resultingemulsions are composed of mixtures of various triglycerides and fattyacids, primarily from fish oil and MCT oil, and are mixed in specificproportions. In either case, when provided within the ranges andspecifications of Table 1, the formulations can yield novel final lipidmixtures that serve as: 1) a dense source of calories, containing: 2) ahighly enriched fish oil as the major lipid source; 3) minimum, butsufficient, amounts of the omega-6 fatty acids; 4) sufficient amounts ofMCT oil to facilitate its metabolic clearance upon intravenous infusion;5) sufficient amounts of MCT oil to facilitate the stability of theemulsion; and/or 6) optionally, a small fraction of soybean oil as anadditional source of essential fatty acids for omega-6 requirements.

In an exemplary embodiment, the concentration of oil in the emulsion canbe any suitable concentration. For example, the final concentration ofoil in the formulation can be 20% oil-in-water or 20 g per 100 mL ofemulsion. More generally, for example, the amount of the oil componentin the oil-in-water emulsion can be from 5 g/100 mL to 30 g/100 mL. Inan exemplary embodiment, the amount of the oil component in theoil-in-water emulsion can be 5 g/100 mL to 17.5 g/100 mL, or the amountof the oil component in the emulsion can be 22.5 g/100 mL to 30 g/100mL.

The composition of the final formulation can be customized to optimizethe ratios of all ingredients to address a wide array of clinical andpharmaceutical issues. In addition, a given formulation may alsodesirably contain a specific ingredient, or set of specific ingredients,for the purpose of addressing one or more particular medical conditionsand/or pharmaceutical purposes, thus yielding several variations incomposition to produce several different formulations. For example, inthe treatment of critically ill patients with systemic inflammatoryresponse syndrome, providing relatively high amounts of omega-3 acidtriglycerides can, for example, counter the deleterious effects ofexcessive inflammation. As well, pharmaceutical benefits can be derivedfrom fish oil containing high concentrations of the bioactive n3-FAs,for example, when used as a drug carrier vehicle to counter the effectsof drugs affecting vital end organs such as nephrotoxicities, so thatrenal blood flow can be maintained by the countervailing effects of theprostaglandins derived from the “3-series” versus deleterious ischemiceffects from the “2-series”. Exemplary ranges of fish oil and MCT oilconcentrations are set forth in Table 1. The specific concentrations ofthe emulsion constituents can depend on the desired treatment.

Table 2 provides a sample of various oil combinations, expressed asweight percentages of each of the triglycerides. In an exemplaryembodiment, only highly-enriched fish oil, in compliance with EPmonograph 1352 (EP 1352, 2008), can be the fish oil source along with acertain amount of MCT oil, also in compliance with EP monograph 0868 (EP0868, 2008), to comprise the total lipid fraction (for example, 20 g ofoil per 100 mL of emulsion) in the current application. In an exemplaryembodiment, a reduced concentration of saturated LCFAs can be employedto avoid potential complications such as insulin resistance (Lee et al,2006), which can be one clinical issue of interest to the criticallyill.

In an exemplary embodiment, the oil component of the emulsion caninclude a vegetable oil. The vegetable oil can include, for example,soybean oil, safflower oil and/or a combination thereof. The vegetableoil can be present in an amount of up to 10%, or from about 1% to about10%, or from about 2% to about 9%, or from about 3% to about 8%, or fromabout 4% to about 7%, or from about 5% to about 6%, based on the weightof the oil component of the emulsion. For example 2 g of vegetable oilsuch as soybean oil can be present per 20 g of total oil per 100 mL ofemulsion.

The vegetable oil, such as soybean oil, can be employed in the eventthat use thereof is deemed clinically advantageous or necessary toincrease the dose of the omega-6 FAs in a given formulation. Forexample, the use of a vegetable oil such as soybean oil can beadvantageous to provide additional nutritional support. For example, thevegetable oil such as soybean oil can be used in the treatment of apatient requiring lifelong intravenous nutrition support where, forexample, meeting the n6-FA requirements of these patients solely viafish oil in fish oil-MCT mixtures may not be sufficient to avoid adeficiency state especially when all nutritional ingredients can only beprovided via the intravenous route of administration.

In exemplary embodiments, the amount of vegetable oil (such as, forexample, soybean oil and/or safflower oil) can be restricted to compriseno more than about 10% by weight of the total oil component, whereas incurrent formulations, concentrations of vegetable oil vary typicallyfrom 20 to 100% by weight of the oil component of the emulsion. Forexample, the vegetable oil can be present from 0% to about 10%, or fromabout 1% to about 9%, or from about 2% to about 8%, or from about 3% toabout 7%, or from about 4% to about 6% based on the total weight of theoil component of the emulsion. There are numerous combinations andpermutations that can be derived from the present compositions.Therefore, it should be understood that those specific combinationsrepresented in Table 2 are merely intended to illustrate representativecombinations and are not meant to be inclusive or restrictive in anyway. Hence, the possibility of additional variations would be clear tothose skilled in the art.

For example, the fish oil emulsion intended in this application can beone that contains a high concentration or the highest concentrationpossible of the bioactively important n3-FAs, which are best able todeliver a wide range of potential clinical benefits by altering lipidsin the blood and the structure and function of cell membranes. Forexample, Increasing the absolute intakes of n3-FAs in order to improvecardiovascular health can be a clinical benefit, for example, ratherthan basing treatment on the n6:n3 ratio as originally thought (StanleyJC et al., 2007), and can be effective to achieve similar clinicalbenefits in other inflammatory conditions. Providing higher amounts ofn3-FAs in relation to n6-FA intakes can result in displacement of AA incell membranes by EPA, and a shift away from the highly vasocactive andpro-inflammatory eicosanoids of the “2-series” in favor of the lessvasoactive “3-series”. These actions can lead to a favorable modulationof the metabolic and immune response to injury and infection,particularly in various scenarios in the acute care setting (e.g.,multiple organ failure, head trauma, sepsis, burns and inflammatorybowel disease). Thus, the source (and subsequent dose) of fish oilintended in this application can have substantial and clinicallybeneficial effects. The fish oil triglycerides can include omega-3 fattyacids, expressed as triglycerides, in an amount of at least 60%, basedon the total weight of the fatty acids of the fish oil triglycerides.The fish oil triglycerides can include a total amount of EPA and DHA,expressed as triglycerides, of at least 45%, based on the total weightof the fatty acids of the fish oil triglycerides. In an exemplaryembodiment, the fish oil triglycerides can include a total amount of EPAand DHA, expressed as triglycerides, of at least 45%, based on the totalweight of the fatty acids of the fish oil triglycerides. For example,the minimum concentration specified can be equal to the sum of EPA andDHA, expressed as triglycerides,≧45% of the n3-FA profile, and the totaln3-FA content (e.g., EPA+DHA+DPA)≧60% by weight from the selected fishoil source. This specification is in conformance with the requirementsof EP monograph 1352 (EP 1352, 2008). Of the three current, commerciallyavailable products containing fish oil, two comply with the lower limits(i.e., EPA≧13%; DHA≧9%; Total n3-FA≧28%) associated with EP monograph1912 (EP 1912, 2008). The concentration of fish oil in the onlycurrently available formulation that meets EP 1352 is only 10% by weightof the oil component of the emulsion, whereas in this application, forexample, the minimum percentage by weight of the oil component of theemulsion containing the specified highly enriched fish oil source can be31%. The amount of bioactive n3-FAs in fish oil described in thisdisclosure can be more than double the amounts more commonly found forclinical use as specified by weight of oil source in the two differentEP monographs (e.g., EP 1352, total n3-FA:≧60%; vs. EP 1912, totaln3-FA:≧28%).

One aspect of an exemplary formulation is to deliver a highconcentration of enriched fish oil triglycerides having, for example,the highest concentration available that meets a high standard or thehighest pharmacopeial standards, for example, in order to maximize theclinical benefits of the n3-FAs in a variety of clinical conditions,such as the systemic inflammatory response syndrome, or SIRS,characteristically found in critically ill patients. In fact, the bloodconcentrations of C-reactive protein, a biomarker of SIRS, was found tobe significantly reduced in critically ill patients with pancreatitisreceiving n3-FAs, as compared to those patients receiving lipids asn6-FAs (Wang, 2008). As inflammation accompanies all forms of acutemetabolic stress, the delivery of highly concentrated n3-FAs may reduceinflammation and improve outcome in the treatment of many medicalconditions. Moreover, since fluid overload is also a major problem inthe intensive care unit, use of highly concentrated n3-FAs would reducethe volume burden, an important clinical issue in the care of criticallyill patients (Lowell et al, 1990). In addition, the total dose of lipidsdelivered would be only one-half the amount according to this disclosurefor current emulsions that conform to EP 1912, compared to using a fishoil source as detailed in this application that meets the higherspecifications of EP 1352, thus, for example, reducing or avoidingexcessive lipid intakes (both quantitiy and quality of fatty acidsdelivered) that may affect its metabolic clearance.

Exemplary formulations described in this disclosure can be designed tocontain a sufficient amount of the essential FAs associated with (orobtained from): 1) the n3 family, i.e., EPA (20:5n3), DHA (22:6n3) andsmall amounts of its precursor, linolenic acid (18:3n3); and, 2) theomega-6, or n6, family, arachidonic acid (20:4n6), or AA, as well assmall amounts of its precursor, linoleic acid (18:2n6). With regard tomeeting the essential n3-FA requirements, this goal can be easily met byboth the recommended concentrations of fish oil in the formula, as wellas from a highly enriched source of n3-FAs, as per the specifications ofEP 1352. The amount of the essential n6-FAs employed can be specificallydesigned to be minimized in exemplary formulations, but in modestamounts that are still large enough to prevent EFA deficiency. Forexample, meeting the n-6 FA requirements can be achieved through the useof a fish oil-MCT mixture, owing to the fact that the average amount ofAA found in fish oil is approximately 0.5%. Therefore, because theamount of FA needed as AA is approximately one-tenth the dose requiredif provided through its precursor, LA, EFA requirements are thus met.For example, to prevent EFA deficiency by providing LA by parenteraladministration, at least 1% of the total daily caloric intake should beprovided (Bistrian, 2003). As stated previously, in a 2000 kcal per daydiet, the minimum intake of LA would be 2.2 g per day, or approximately3.5 g of soybean oil (˜55% LA); in terms of AA, the requirements for thesame diet would be approximately 0.2 g per day; in a 1500 kcal per daydiet, 1.6 g of LA, or˜ 0.16 g of AA, per day would be needed; in a 1000kcal per day diet, 1.1 g of LA, or˜ 0.11 g of AA, would be needed; in a500 kcal per day diet, 0.55 g of LA, or ˜0.05 g of AA would be needed;and finally, in a 100 kcal per day diet, 0.11 g of LA would be needed,or 0.01 g as AA per 100 calories. As can be seen in Table 3, whichprovides sample compositions for Fish Oil-MCT mixtures only, the EFArequirements for n6-FAs, coming from AA in the fish oil, would be met inthe 80% fish oil-20% MCT oil mixture as presented. This does not includethe additional source of n6-FAs that comes from the LA normally presentin fish oil. It should also be recognized that certain compositions orformulations of products derived from this description, for example, canbe intended for short-term parenteral administration during criticalillness, for example, rather than for patients susceptible to EFAdeficiency. In other cases, where EFA supplementation is a clinicalconcern, alternative formulations can be devised that contain very lowamounts of soybean oil (for example, up to 10%) of the total oil phase.Table 4 provides exemplary formulations using a fixed 60:40 ratio (byweight) of fish oil to MCT oil, with increasing fractions of soybeanoil, ranging from 1 to 5%. The “fixed” fish oil-MCT ratio shown in Table4 is merely illustrative and not meant to be exclusive or restrictive inany way as to the various oil ratios that are possible based on thisdisclosure.

An exemplary final concentration of oil in exemplary formulations is a20% oil-in-water emulsion (20 g oil mixture per 100 mL of emulsion).This overall oil concentration can be consistent with the oilconcentration in administered lipid emulsions used clinically, and itcan be associated with better plasma clearance compared to “10%”formulations, as the optimum phospholipid-triglyceride (PL:TG) ratio forparenteral lipid emulsions appears to be about 0.06 (1.2 g PL:20 g TG)(Driscoll et al., 2001). Nonetheless, there are multiple variations inthe final concentration of oil in mixtures that can be devised inexemplary embodiments, as long as the PL:TG ratio of 0.06 is maintained.A sample of the possible formulations is shown in Table 5.

The concentrations of MCT oil in various possible formulations can besufficient to facilitate the clearance of the long-chain triglyceridesin fish oil (20-carbon EPA and 22-carbon DHA), which has been shown tooccur in other mixtures (Simoens et al., 2008). Exemplary ratios (byweight) of MCT to omega-3 LCT in this application can be different fromthat found in other parenteral lipid emulsion mixtures containing bothof these oils. For this reason, exemplary amounts described in thisapplication are unique and the resulting formulations can benefit fromassessment to confirm the favorable effect on plasma clearance of LCTsin the presence of MCTs. Additionally or alternatively, the clearance ofthese formulations can be facilitated by optimizing the infusion rate,for example, in accordance with its normal metabolic clearance.

The concentrations of MCT oil in the various possible formulations canbe sufficient to facilitate the physicochemical stability of thelong-chain triglycerides in fish oil (20-carbon EPA and 22-carbon DHA),which has been shown to occur in other mixtures. (Driscoll et al.,2002). Exemplary ratios (by weight) of MCT to omega-3 LCT described inthis application can be different from other parenteral lipid emulsionmixtures containing both of these oils. For this reason, the relativeand absolute amounts of each type of oil that are used in thisapplication can be unique and the resulting formulations can benefitfrom assessment to confirm the favorable effect on emulsion stability ofLCTs in the presence of MCTs.

In an exemplary embodiment, the amounts of saturated LCFAs in anemulsion can be modified, for example, so as to lower the concentrationthereof from what is present in natural sources. For example, a specificreduction in the concentrations of LCFAs, such as palmitic acid (16:0),can help to reduce the risk of insulin resistance (Lee et al, 2006),which can be particularly relevant in acutely ill patients. In addition,for example, by effectively increasing the proportion of highly enrichedpolynsaturated n3-FAs, such as EPA (20:5n3) and DHA (22:6n3), inaccordance with EP 1352, and by increasing the proportion of the highlyenriched fish oil triglycerides in the oil component of the emulsion asdescribed, this can reduce the concentrations of the saturated LCFAsthat can produce potentially deleterious adverse effects.

Exemplary parenteral lipid emulsions can optionally contain vegetableoil as an additional source of n6-FAs, in addition to the amountsalready present in the fish oil. For example, the soybean oil can bepresent as a very small fraction (by weight of the oil component of theemulsion). The soybean oil can be employed, for example, in a case whereEFA deficiency is considered to pose a significant clinical risk, suchas in patients receiving life-long parenteral nutrition support. In thispatient population, nutrient deficiencies can develop, for example, ifthere is little to no gastrointestinal absorption of nutrients via oralintake. In this circumstance, a higher intake of n6-FAs via parenterallipid emulsion may be desirable. Table 4 provides an exemplary sample ofpossible formulations, where the soybean oil content is increasedprogressively up to a level of 5% by weight of the oil component of theemulsion. In addition, the use of higher n3-FA proportions (up to 90%)in various possible formulations can, for example, also increase n6-FAintake.

Exemplary formulations produced as described herein can be designed toprovide a unique, but dense, source of calories that are, for example,equally nitrogen-sparing as in conventional or current parenteral lipidemulsions. The final parenteral lipid formulation can ideally be anisotonic energy source that can be provided in small volumes whenpossible. This can be particularly advantageous, for example, in thecase of acutely ill patients who may be volume-overloaded as a result ofreceiving multiple intravenous fluids for medical purposes, such as forresuscitation and maintenance of blood pressure, kidney function andintravenous medications.

According to an exemplary aspect, a composition comprising an enrichedfish oil triglycerides as a lipid source is provided.

In another exemplary aspect, the composition comprises at least 45% byweight of EPA and DHA, expressed as triglycerides, and at least 60% byweight of n3-FA, expressed as triglycerides, based on the total weightof the composition.

In another exemplary aspect, the composition is an oil-in-water emulsionhaving an oil derived from an enriched fish oil of from about 31% toabout 90% by weight of the oil component of the emulsion.

In another exemplary aspect, a method of administering the composition(such as, for example, an emulsion) is provided comprising administeringthe composition to a human body, wherein the oil component of theemulsion contains a sufficient concentration of n3-FAs to provide aneffective dose.

In other exemplary aspects, the administered dose of n3-FAs is capableof the safe treatment of systemic inflammatory response syndrome (SIRS);the dose is capable of the safe treatment of respiratory distresssyndrome (RDS); the dose is capable of the safe treatment ofnutritional/dietary causes of liver disease; the dose is capable of thesafe treatment of iatrogenic causes of liver or kidney disease; the doseis capable of the safe treatment of pathological causes of liver orkidney disease; the dose is capable of the safe treatment of immunemodulation; the dose is capable of the safe treatment of head trauma;the dose is capable of the safe treatment of postoperative surgicalstress; the dose is capable of the safe treatment of myocardialinfarction; and/or the dose is capable of the safe treatment of cysticfibrosis.

In another exemplary aspect, a composition is provided comprisingomega-3 essential fatty acids and omega-6 essential fatty acids of afish oil, wherein the essential fatty acids are present in amountseffective to minimize an impact of excessive amounts of pro-inflammatoryfatty acids.

In another exemplary aspect, a method of administering the compositionis provided comprising administering the composition to a human body.

In another exemplary aspect, an amount of the omega-6 essential fattyacid is capable of the safe treatment to mitigate or prevent EFAdeficiency when the range of fish oil is from 31% and 90%, by weight ofthe oil component of the emulsion, in the absence of soybean oil.

In another exemplary aspect, an amount of the omega-6 essential fattyacid is capable of the safe treatment for mitigation or prevention ofEFA deficiency when the range of concentration of fish oil triglyceridesis from about 31% to about 90% by weight of the oil phase of theemulsion in the absence of soybean oil. To further mitigate or preventEFA deficiency when the range of fish oil is between 31% and 90%, theconcentration of additional soybean oil can be between 1 and 10%, byweight of the oil component of the emulsion.

In another exemplary aspect, an amount of the omega-6 essential fattyacid is capable of the safe treatment of medical conditions withoutexerting clinically significant adverse effects related to eicosanoidmetabolism.

In another exemplary aspect, an amount of the omega-6 essential fattyacid does not interfere with or counteract the dose of n3-FAs present.

In another exemplary aspect, a composition is provided comprisingmedium-chain fatty acids of an MCT oil, wherein the medium-chain fattyacids are present in an amount effective to facilitate a metabolicclearance of fish oil.

In another exemplary aspect, the MCT oil is present in an amount of fromabout 10% to about 69%, by weight of the oil component of the emulsion,and the amount of the MCT oil allows for the safe plasma clearance ofthe fish oil.

In other exemplary aspects, the dose of lipids infused is incorporatedinto cell membranes; the dose of lipids infused generates eicosanoids ofthe 3-series; and/or the dose of lipids infused does not produceclinically significant hypertriglyceridemia.

In another exemplary aspect, a composition is provided comprisingmedium-chain triglycerides of an oil, wherein the medium-chaintriglycerides are present in an amount effective to facilitatestability.

In another exemplary aspect, a composition is provided wherein the MCToil concentration is from about 10% to about 69%, by weight of the oilcomponent of the emulsion, and the fish oil concentration is from about31% to about 90%, by weight of the oil component of the emulsion, andwherein the concentrations allow for physicochemical stability of thecomposition for from about 18 to about 24 months.

In another exemplary aspect, the MCT oil concentration is from about 10%to about 69%, the fish oil concentration is from about 31% to about 90%,by weight of the oil component of the emulsion, and a soybean oilconcentration is up to about 10%, by weight of the oil component of theemulsion, and wherein the concentrations allow for physicochemicalstability of the composition in its original container for from about 18to about 24 months.

In another exemplary aspect, the MCT oil concentration is from about 10%to about 69%, by weight of the oil component of the emulsion, and thefish oil concentration is from about 31% to about 90%, by weight of theoil component of the emulsion, and wherein the concentrations allow forphysicochemical stability of the composition as used in anextemporaneously prepared syringe for up to 12 hours at temperatures upto 40° C.

In another exemplary aspect, the MCT oil concentration is from about 10%to about 69%, by weight of the oil component of the emulsion, and thefish oil concentration is from about 31 to about 90%, by weight of theoil component of the emulsion, and a soybean oil concentration is up toabout 10%, for example up to about 5%, by weight of the oil component ofthe emulsion, wherein the concentrations allow for the physicochemicalstability of the composition as used in an extemporaneously preparedsyringe for up to 12 hours at temperatures up to 40° C.

In another exemplary aspect, the MCT oil concentration is from about 10%to about 69%, by weight of the oil component of the emulsion, and thefish oil concentration is from about 31% to about 90%, by weight of theoil component of the emulsion, and the concentrations allow for thephysicochemical stability of the composition as an extemporaneously TPNadmixture for up to 24 hours at temperatures up to 40° C.

In another exemplary aspect, the MCT oil concentration is from about 10%to about 69%, by weight of the oil component of the emulsion, the fishoil concentration is from about 31% to about 90%, by weight of the oilcomponent of the emulsion, and a soybean oil concentration is up to 10%,by weight of the oil component of the emulsion, and the concentrationsallow for the physicochemical stability of the composition as used in anextemporaneously prepared TPN admixture for up to 24 hours attemperatures up to 40° C.

In another exemplary aspect, the composition provides a source ofcalories that is equally nitrogen-sparing as a soybean parenteraloil-in-water emulsion.

In another exemplary aspect, the composition provides a sufficientamount of egg phospholipids in proportion to the triglyceride oil phase,in order to stabilize the emulsion.

In another exemplary aspect, the composition provides a sufficientamount of egg phospholipids in proportion to the triglyceride oil phase,in order to not interfere with the clearance or breakdown of the infusedlipid droplets.

In another exemplary aspect, the composition provides a sufficientamount of α-tocopherol as an anti-oxidant to protect the highlypolyunsaturated n-3 fatty acids present.

In another exemplary aspect, a composition is provided comprising fattyacids of a fish oil and medium-chain triglycerides, wherein thecomposition is an oil-in-water emulsion comprising an oil phase and anaqueous phase.

In another exemplary aspect, the enriched fish oil is present in anamount from about 31% to about 90%, by weight of the oil component ofthe emulsion.

In another exemplary aspect, the medium-chain triglycerides are ispresent in an amount from about 10% to about 69%, by weight of the oilcomponent of the emulsion.

In another exemplary aspect, a method of parenteral administration ofthe composition is provided comprising parenterally administering thecomposition to a human body.

The examples described herein are not meant to be inclusive, but insteadhave been utilized in order to form exemplary embodiments of thedisclosure. It should be understood that manipulation of specificconcentrations of total ingredients, including, for example, specificcompositions and proportions of each ingredient within the specifiedconcentration ranges, may be advantageous in order to achieve a specificoptimal outcome. In the present disclosure, exemplary aspects can yieldunique parenteral lipid emulsions appropriate for special medicalpurposes.

As already described herein, exemplary emulsions can have various finalcompositions and characteristics depending on the specific applicationof the emulsion. In an exemplary embodiment, the emulsion can be incompliance with the specifications set forth in United StatesPharmacopoeia (USP) Chapter <729> entitled “Globule Size Distribution inLipid Injectable Emulsions” (United States Pharmacopoeia, 2009), thecontents of which are incorporated herein by reference. The twoexemplary globule size limits include: 1) the intensity-weighted meandroplet size that is less 500 nanometers obtained by dynamic or staticlight scattering methods; and, 2) the volume-weighted percent of fatgreater than five micrometers or PFAT5 that is less than 0.05% obtainedby light extinction employing single-particle optical sensing methods.

The emulsion can have any suitable physical and chemical characteristicssuch as droplet size, and pH, free fatty acids, etc. For example, theemulsion can possess physical characteristics which facilitate its usein parenteral administration applications. In an exemplary embodiment,an emulsion can have a mean droplet size of, for example, less than 500nm, or less than 250 nm, or less than 240 nm, or from 230 to 240 nm. Inan exemplary embodiment, an emulsion can have a PFAT₅ value of less than0.05%.

Exemplary physical and chemical embodiments were prepared and tested toconfirm that such embodiments comply with specifications, for example,specification set forth in USP <729> and exemplary manufacturingspecifications. To exemplify the pharmaceutical feasibility of theexemplary emulsions containing relatively high amounts of omega-3 acidtriglycerides, for example, about 60% to about 90% by weight of the oilcomponent, along with relatively low amounts of MCT, for example, about10% to about 40% by weight of the oil phase, exemplary lipid emulsions 1and 2 were manufactured and tested having omega-3 fatty acidtriglycerides-to-MCTs ratios of 90:10, and 70:30, respectively, werecompared to currently available emulsions 3, 4 and 5. Various physicaland chemical characteristics were measured and compared, and the resultsare set forth in Table 6.

As can be seen from the results, like currently available emulsions, theexemplary emulsions were in compliance with the mean size and PFAT₅specifications of the United States Pharmacopoeia (USP) Chapter <729>entitled “Globule Size Distribution in Lipid Injectable Emulsions”(United States Pharmacopoeia, 2009). In addition, exemplary emulsionswere in compliance with exemplary manufacturing specifications (forexample pH, peroxide value, acid value, free fatty acids, phosphatidylcholine and glycerol). Such data confirms Applicant's priorunderstanding that exemplary emulsions are capable of compliance withvarious specifications.

Tables mentioned herein are set forth below:

TABLE 1 Compositions of LipOmega-3 MCT 20% CONCENTRATION ***RANGE OF*PHARMACEUTICAL (g/L) **(80% CONCENTRATIONS INGREDIENT F.O.:20% MCT)(g/L) Fish Oil Major FAs 160  62 to 180 (36.5%) EPA (20:5n3) 58.4 22.6to 65.7 (25.3%) DHA (22:6n3) 40.5 15.7 to 45.5 (7.0%) DPA (20:6n3) 11.1 4.0 to 12.6 (0.50%) AA (20:4n6) 0.8 0.31 to 0.9  MCT Oil 40  20 to 138Soybean Oil Major FAs 0  0 to 10 (55%) (18:2n6) 0 0.0 to 5.5 (10%)(18:3n3) 0 0.0 to 1.0 Glycerol 22.5 20 to 25 Egg Phospholipids 12 PL:TGRatio, 0.06 Sodium Oleate 2.5 0 to 3 α-tocopherol 0.2 0 to 1 SterileWater for Inj. q.s. ad 1000.0 Fixed *INGREDIENT Ranges: Fish Oil: 31 to90%; MCT Oil: 10 to 69%; Soybean Oil: 0 to 5%; Glycerol: 2.0 to 2.5%;**Sample Formulation and g per L ***GENERAL CALCULATED RANGE: RANGES ofIngredients; not accounting for experimental errors in measurement.

TABLE 2 Sample Compositions of Possible Oil Combinations of LipOmega-3MCT 20% Sample Fish Oil (%) MCT Oil (%) Soybean Oil (%) 1 90 10 0 2 8020 0 3 70 30 0 4 60 40 0 5 50 50 0 6 40 60 0 7 31 69 0 8 90 9 1 9 80 182 10 70 27.5 2.5 11 60 37 3 12 50 46.5 3.5 13 40 56 4 14 31 64 5

TABLE 3 EFA Intakes from Sample LipOmega-3 MCT Formulations Fish Oil-MCTOil Mixtures Kcals/day (20% Fat) *Linoleic 2.2% *Linolenic 1.5% AA EPADHA 20 g (100 mL) of a Fish Oil 80% - MCT Oil 20% Mixture  100 (2.2 g)0.038 g 0.026 g 0.009 g 0.64 g 0.45 g  500 (11.1 g) 0.195 g 0.133 g0.044 g 3.24 g 2.25 g 1000 (22.2 g) 0.391 g 0.266 g 0.089 g 6.48 g 5.62g 1500 (33.3 g) 0.586 g 0.399 g 0.133 g 9.72 g 8.42 g 2000 (44.4 g)0.781 g 0.533 g 0.178 g 12.96 g  11.23 g  20 g (100 mL) of a Fish Oil70% - MCT Oil 30% Mixture  100 (2.2 g) 0.033 g 0.023 g 0.008 g 0.56 g0.39 g  500 (11.1 g) 0.171 g 0.117 g 0.039 g 2.84 g 1.97 g 1000 (22.2 g)0.342 g 0.233 g 0.078 g 5.67 g 3.93 g 1500 (33.3 g) 0.513 g 0.350 g0.117 g 8.51 g 5.90 g 2000 (44.4 g) 0.684 g 0.466 g 0.155 g 11.34 g 7.86 g 20 g (100 mL) of a Fish Oil 60% - MCT Oil 40% Mixture  100 (2.2g) 0.029 g 0.020 g 0.007 g 0.48 g 0.33 g  500 (11.1 g) 0.147 g 0.100 g0.033 g 2.43 g 1.68 g 1000 (22.2 g) 0.293 g 0.200 g 0.067 g 4.86 g 3.37g 1500 (33.3 g) 0.440 g 0.300 g 0.100 g 7.29 g 5.05 g 2000 (44.4 g)0.586 g 0.400 g 0.133 g 9.72 g 6.74 g 20 g (100 mL) of a Fish Oil 50% -MCT Oil 50% Mixture  100 (2.2 g) 0.024 g 0.017 g 0.006 g 0.40 g 0.28 g 500 (11.1 g) 0.122 g 0.083 g 0.028 g 2.03 g 1.40 g 1000 (22.2 g) 0.244g 0.167 g 0.056 g 4.05 g 2.81 g 1500 (33.3 g) 0.366 g 0.250 g 0.083 g6.08 g 4.21 g 2000 (44.4 g) 0.488 g 0.333 g 0.111 g 8.10 g 5.62 g 20 g(100 mL) of a Fish Oil 40% - MCT Oil 60% Mixture  100 (2.2 g) 0.019 g0.013 g 0.004 g 0.32 g 0.22 g  500 (11.1 g) 0.098 g 0.067 g 0.022 g 1.62g 1.12 g 1000 (22.2 g) 0.195 g 0.133 g 0.044 g 3.24 g 2.25 g 1500 (33.3g) 0.293 g 0.200 g 0.067 g 4.86 g 3.37 g 2000 (44.4 g) 0.391 g 0.266 g0.089 g 6.48 g 4.49 g *Amounts of omega-6 FAs are averages from fishfamilies in monograph 1352.

TABLE 4 EFA Intakes from Sample LipOmega-3 MCT Formulations Fish Oil-MCTOil-Soya Oil Mixtures Kcals/day (20% Fat) *Linoleic *Linolenic AA EPADHA 20 g (100 mL) of Fish Oil 60% - MCT Oil 39% - Soya Oil 1%  100 (2.2g) 0.041 g 0.022 g 0.007 g 0.48 g 0.33 g  500 (11.1 g) 0.208 g 0.110 g0.033 g 2.43 g 1.68 g 1000 (22.2 g) 0.415 g 0.222 g 0.067 g 4.86 g 3.37g 1500 (33.3 g) 0.623 g 0.333 g 0.100 g 7.29 g 5.05 g 2000 (44.4 g)0.830 g 0.444 g 0.133 g 9.72 g 6.74 g 20 g (100 mL) of Fish Oil 60% -MCT Oil 38% - Soya Oil 2%  100 (2.2 g) 0.053 g 0.024 g 0.007 g 0.48 g0.33 g  500 (11.1 g) 0.269 g 0.122 g 0.033 g 2.43 g 1.68 g 1000 (22.2 g)0.537 g 0.244 g 0.067 g 4.86 g 3.37 g 1500 (33.3 g) 0.806 g 0.367 g0.100 g 7.29 g 5.05 g 2000 (44.4 g) 1.074 g 0.489 g 0.133 g 9.72 g 6.74g 20 g (100 mL) of Fish Oil 60% - MCT Oil 37% - Soya Oil 3%  100 (2.2 g)0.065 g 0.027 g 0.007 g 0.48 g 0.33 g  500 (11.1 g) 0.330 g 0.133 g0.033 g 2.43 g 1.68 g 1000 (22.2 g) 0.659 g 0.266 g 0.067 g 4.86 g 3.37g 1500 (33.3 g) 0.989 g 0.400 g 0.100 g 7.29 g 5.05 g 2000 (44.4 g)1.319 g 0.533 g 0.133 g 9.72 g 6.74 g 20 g (100 mL) of Fish Oil 60% -MCT Oil 36% - Soya Oil 4%  100 (2.2 g) 0.077 g 0.029 g 0.007 g 0.48 g0.33 g  500 (11.1 g) 0.391 g 0.144 g 0.033 g 2.43 g 1.68 g 1000 (22.2 g)0.781 g 0.289 g 0.067 g 4.86 g 3.37 g 1500 (33.3 g) 1.173 g 0.433 g0.100 g 7.29 g 5.05 g 2000 (44.4 g) 1.563 g 0.578 g 0.133 g 9.72 g 6.74g 20 g (100 mL) of Fish Oil 60% - MCT Oil 35% - Soya Oil 5%  100 (2.2 g)0.085 g 0.031 g 0.007 g 0.48 g 0.33 g  500 (11.1 g) 0.452 g 0.156 g0.033 g 2.43 g 1.68 g 1000 (22.2 g) 0.904 g 0.311 g 0.067 g 4.86 g 3.37g 1500 (33.3 g) 1.356 g 0.467 g 0.100 g 7.29 g 5.05 g 2000 (44.4 g)1.807 g 0.622 g 0.133 g 9.72 g 6.74 g *Includes amounts from both FishOil and Soya Oil.

TABLE 5 Various Sample Concentrations of the Oil Phase While Maintaininga Phospholipid:Triglyceride ratio of 0.06 Total Oil Phospholipid FishOil MCT Oil Soya Oil (g/100 mL) (g/100 mL) (%) (%) (%) 5.0 0.30 90 10 07.5 0.45 80 20 0 10.0 0.60 80 15 5 12.5 0.75 70 30 0 15.0 0.90 70 29 117.5 1.05 60 40 0 20.0 1.20 60 36 4 22.5 1.35 50 50 0 25.0 1.50 50 47 327.5 1.65 40 60 0 30.0 1.80 31 69 0

TABLE 6 Physical and Chemical Profile of Exemplary and ComparativeEmulsions (20 g oil/dL) at 25° C. Specifications Emulsions ParameterRange 1 2 3 4 5 pH 7.5-8.5 8.07 8.06 8.1 8.0 7.9 Mean Size 240-320 234235 282 243 256 (nm) PFAT₅ (%) <0.05 0.042 0.034 0.029 0.018 0.025Peroxide ≦1.0 0.38 0.40 <0.1 <0.1 <0.1 Value Acid Value ≦0.5 0.14 0.12<0.2 0.3 0.3 Free Fatty ≦3.0 2.28 1.91 1.98 2.17 2.23 Acids (mmol/L)Phosphatidyl  7.8-10.6 9.53 9.91 9.13 8.89 9.13 Choline (g/L) Glycerol23.8-26.3 24.5 25.2 25.6 25.3 25.8 (g/L) 1 (exemplary) = 90% Fish OilTriglycerides (FOT): 10% Medium Chain Triglycerides (MCTs) 2 (exemplary)= 70% FOT: 30% MCTs 3 (comparative) = Lipofundin N (100% Soybean OilTriglycerides) 4 (comparative) = Lipofundin MCT (50% Soybean OilTriglycerides: 50% MCTs) 5 (comparative) = Lipidem (50% MCTs: 40%Soybean Oil Triglycerides: 10% FOT)

While various embodiments are described herein, it will be appreciatedthat variations, modifications and other changes in form and detail maybe made without departing from the spirit and scope of the disclosure.Such variations and modifications are to be considered within thepurview and scope of the disclosure as defined by the appended claims.

REFERENCES

-   Lowell et al. Crit Care Med 1990;18:728-733.-   Mathru et al. Chest 1991;99:426-29.-   Prasertsom et al., Arch Dis Child 1996;74:F95-98.-   Ling et al. Digestive Disease Science 2001;46:2484-9.-   Driscoll et al. Lipid Emulsions in Parenteral Nutrition. In Clinical    Nutrition: Parenteral Nutrition (Rombeau, Rolandelli, eds.) W. B.    Saunders, 2001; pp. 35-59.-   Driscoll et al. International Journal of Pharmaceutics,    2002;240:1-10.-   Bistrian, Journal of Parenteral and Enteral Nutrition,    2003;27:168-75.-   Gura et al. Clinical Nutrition 2005;24:839-47.-   Wales et al. Journal of Pediatric Surgery 2005;40:755-62.-   Paquot et al. Curr Opin Clin Nutr Metab Care 2005;8:183-87.-   Lee et al. J Appl Physiol 2006 ;100 :1467-74.-   Gura et al. Pediatrics 2006;118:e197-e201.-   Stanley et al. British Journal of Nutrition, 2007; 98:1305-1310.-   Wanten et al. American Journal of Clinical Nutrition    2007;85:1171-84.-   European Pharmacopoeia 6.0, Monograph 1352, Omega-3 Acid    Triglycerides, Omega-3 acidorum triglyceride, 1893-95, 2008.-   European Pharmacopoeia 6.0, Monograph 1912, Fish Oil, Rich in    Omega-3 Acids, Piscis oleum omega-3 acidis abundans, 2554-56, 2008.-   European Pharmacopoeia 6.0, Monograph 0868, Triglycerides,    Medium-Chain, Triglycerida saturate media, 3122-24, 2008.-   Driscoll et al, International Journal of Pharmaceutics, 2008a, In    press.-   Wang et al. Journa of Parenteral and Enteral Nutrition,    2008;32:236-41.-   Simoens et al. American Journal of Clinical Nutrition    2008;88:282-88.-   Driscoll et al. Parenteral and Enteral Nutrition in the Intensive    Care Unit. In Intensive Care Medicine (Irwin and Rippe, eds.),    Wolters Kluwer, 2008b; pp. 2187-2201.    United States Pharmacopoeia (USP) Chapter <729> entitled “Globule    Size Distribution in Lipid Injectable Emulsions” (United States    Pharmacopoeia, 2009).

All of the references are herein incorporated by reference in theirentirety to the same extent as if each individual reference werespecifically and individually indicated to be incorporated herein byreference in its entirety.

1. An emulsion comprising: an oil component and a water component, theoil component comprising: fish oil triglycerides in an amount of about60% to about 90% based on the weight of the oil component; wherein thefish oil triglycerides comprise omega-3 fatty acids, expressed astriglycerides, in an amount of at least 60%, based on the total weightof the fatty acids of the fish oil triglycerides; wherein the fish oiltriglycerides comprise a total amount of EPA and DHA, expressed astriglycerides, of at least 45%, based on the total weight of the fattyacids of the fish oil triglycerides; and, at least one medium-chaintriglyceride oil, wherein a total amount of the at least onemedium-chain triglyceride oil is from about 10% to about 40% based onthe weight of the oil component.
 2. The emulsion of claim 1, wherein thefish oil triglycerides are present in an amount of about 70% to about90% based on the weight of the oil component of the emulsion.
 3. Theemulsion of claim 1, wherein the fish oil triglycerides are present inan amount of about 80% to about 90% based on the weight of the oilcomponent of the emulsion.
 4. The emulsion of claim 1, wherein the totalamount of the at least one medium-chain triglyceride oil is from about10% to about 30% based on the weight of the oil component of theemulsion.
 5. The emulsion of claim 1, wherein the total amount of the atleast one medium-chain triglyceride oil is from about 10% to about 20%based on the weight of the oil component of the emulsion.
 6. Theemulsion of claim 1, comprising a vegetable oil.
 7. The emulsion ofclaim 6, wherein the vegetable oil is present in an amount of up to 10%based on the weight of the oil component of the emulsion.
 8. Theemulsion of claim 6, wherein the vegetable oil comprises a soybean oil,a safflower and/or a mixture thereof.
 9. The emulsion of claim 1,wherein the oil component is substantially free of myristic acid,palmitic acid and stearic acid.
 10. The emulsion of claim 1, wherein theamount of the oil component in the emulsion is 5 g/100 mL to 17.5 g/100mL, or the amount of the oil component in the emulsion is 22.5 g/100 mLto 30 g/100 mL.
 11. The emulsion of claim 1, comprising eggphospholipid.
 12. The emulsion of claim 1, comprising α-tocopherol. 13.The emulsion of claim 1, comprising an omega-6 fatty acid-containingtriglyceride.
 14. The emulsion of claim 1, wherein the emulsion isphysicochemically stable for at least 18 months.
 15. The emulsion ofclaim 1, wherein the emulsion is physicochemically stable as anextemporaneously prepared syringe dosage for at least 12 hours at atemperature of 40° C.
 16. A method of administering the emulsion ofclaim 1, comprising administering a dose of the emulsion to a humanbody.
 17. A method of parenterally administering the emulsion of claim1, comprising parenterally administering a dose of the emulsion to ahuman body to treat a condition selected from the group consisting of: asystemic inflammatory response syndrome, a respiratory distresssyndrome, a nutritional and/or dietary cause of liver disease, aniatrogenic cause of liver disease, a pathological cause of liverdisease, an immune modulation, head trauma, postoperative surgicalstress, a myocardial infarction, cystic fibrosis and a combinationthereof.
 18. An oil composition suitable for use as an oil component ofan oil-in-water emulsion, comprising: fish oil triglycerides in anamount of about 60% to about 90% based on the weight of the composition;wherein the fish oil triglycerides comprise omega-3 fatty acids,expressed as triglycerides, in an amount of at least 60%, based on thetotal weight of the fatty acids of the fish oil triglycerides; whereinthe fish oil triglycerides comprise a total amount of EPA and DHA,expressed as triglycerides, of at least 45%, based on the total weightof the fatty acids of the fish oil triglycerides; and, at least onemedium-chain triglyceride oil, wherein a total amount of the at leastone medium-chain triglyceride oil is from about 10% to about 40% basedon the weight of the composition.
 19. An emulsion comprising: an oilcomponent and a water component, the oil component comprising: fish oiltriglycerides in an amount of greater than 50% to about 90% based on theweight of the oil component of the emulsion; wherein the fish oiltriglycerides comprise omega-3 fatty acids, expressed as triglycerides,in an amount of at least 60%, based on the total weight of the fattyacids of the fish oil triglycerides; wherein the fish oil triglyceridescomprise a total amount of EPA and DHA, expressed as triglycerides, ofat least 45%, based on the total weight of the fatty acids of the fishoil triglycerides; and, a medium-chain triglyceride oil.
 20. Theemulsion of claim 19, wherein the fish oil triglycerides are present inan amount of about 60% to about 90% based on the weight of the oilcomponent of the emulsion.
 21. The emulsion of claim 19, wherein thetotal amount of the at least one medium-chain triglyceride oil is fromabout 10% to about 40% based on the weight of the oil component of theemulsion.
 22. The emulsion of claim 19, comprising a vegetable oil. 23.The emulsion of claim 22, wherein the vegetable oil is present in anamount of up to 10% based on the weight of the oil component of theemulsion.
 24. The emulsion of claim 22, wherein the vegetable oilcomprises a soybean oil, a safflower and/or a mixture thereof.
 25. Theemulsion of claim 19, wherein the emulsion is an oil-in-water emulsion,and wherein the concentration of the oil component in the emulsion is 5g/100 mL to 17.5 g/100 mL, or the concentration of the oil component inthe emulsion is 22.5 g/100 mL to 30 g/100 mL.
 26. The emulsion of claim19, wherein the emulsion is physicochemically stable for at least 18months.
 27. A method of administering the emulsion of claim 19,comprising administering a dose of the emulsion to a human body.
 28. Anemulsion comprising: an oil component and a water component, the oilcomponent comprising: fish oil triglycerides in an amount of about 31%to about 90% based on the weight of the oil component of the emulsion;wherein the fish oil triglycerides comprise omega-3 fatty acids,expressed as triglycerides, in an amount of at least 60%, based on thetotal weight of the fatty acids of the fish oil triglycerides; whereinthe fish oil triglycerides comprise a total amount of EPA and DHA,expressed as triglycerides, of at least 45%, based on the total weightof the fatty acids of the fish oil triglycerides; and, a medium-chaintriglyceride; wherein the emulsion is an oil-in-water emulsion, andwherein the concentration of the oil component in the emulsion is 5g/100 mL to less than 20 g/100 mL, or the concentration of the oilcomponent in the emulsion is greater than 20 g/100 mL to 30 g/100 mL.29. The emulsion of claim 28, wherein the fish oil triglycerides arepresent in an amount of about 60% to about 90% based on the weight ofthe oil component of the emulsion.
 30. The emulsion of claim 28, whereinthe total amount of the at least one medium-chain triglyceride oil isfrom about 10% to about 40% based on the weight of the oil component ofthe emulsion.
 31. The emulsion of claim 28, comprising a vegetable oil.32. The emulsion of claim 31, wherein the vegetable oil is present in anamount of up to 10% based on the weight of the oil component of theemulsion.
 33. The emulsion of claim 31, wherein the vegetable oilcomprises a soybean oil, a safflower and/or a mixture thereof.
 34. Theemulsion of claim 28, wherein the concentration of the oil component inthe emulsion is 5 g/100 mL to 17.5 g/100 mL, or the concentration of theoil component in the emulsion is 22.5 g/100 mL to 30 g/100 mL.
 35. Theemulsion of claim 28, wherein the emulsion is physicochemically stablefor at least 18 months.
 36. A method of administering the emulsion ofclaim 28, comprising administering a dose of the emulsion to a humanbody.
 37. An emulsion comprising: an oil component and a watercomponent, the oil component comprising: fish oil triglycerides presentin an amount of about 31% to about 90% based on the weight of the oilcomponent of the emulsion; wherein the fish oil triglycerides compriseomega-3 fatty acids, expressed as triglycerides, in an amount of atleast 60%, based on the total weight of the fatty acids of the fish oiltriglycerides; wherein the fish oil triglycerides comprise a totalamount of EPA and DHA, expressed as triglycerides, of at least 45%,based on the total weight of the fatty acids of the fish oiltriglycerides; a medium-chain triglyceride oil; and a vegetable oil. 38.The emulsion of claim 37, wherein the fish oil triglycerides are presentin an amount of about 60% to about 90% based on the weight of the oilcomponent of the emulsion.
 39. The emulsion of claim 37, wherein thetotal amount of the at least one medium-chain triglyceride oil is fromabout 10% to about 40% based on the weight of the oil component of theemulsion.
 40. The emulsion of claim 37, wherein the vegetable oil ispresent in an amount of up to 10% based on the weight of the oilcomponent of the emulsion.
 41. The emulsion of claim 37, wherein thevegetable oil comprises a soybean oil, a safflower and/or a mixturethereof.
 42. The emulsion of claim 37, wherein the emulsion is anoil-in-water emulsion, and wherein the concentration of the oilcomponent in the emulsion is 5 g/100 mL to 17.5 g/100 mL, or theconcentration of the oil component in the emulsion is 22.5 g/100 mL to30 g/100 mL.
 43. The emulsion of claim 37, wherein the emulsion isphysicochemically stable for at least 18 months.
 44. A method ofadministering the emulsion of claim 37, comprising administering a doseof the emulsion to a human body.
 45. An emulsion comprising: an oilcomponent and a water component, the oil component comprising: fish oiltriglycerides present in an amount of about 31% to about 90% based onthe weight of the oil component of the emulsion; wherein the fish oiltriglycerides comprise omega-3 fatty acids, expressed as triglycerides,in an amount of at least 60%, based on the total weight of the fattyacids of the fish oil triglycerides; wherein the fish oil triglyceridescomprise a total amount of EPA and DHA, expressed as triglycerides, ofat least 45%, based on the total weight of the fatty acids of the fishoil triglycerides; and, a medium-chain triglyceride oil; wherein theemulsion is an oil-in-water emulsion, and wherein the concentration ofthe oil component in the emulsion is 5 g/100 mL to 17.5 g/100 mL, or theconcentration of the oil component in the emulsion is 22.5 g/100 mL to30 g/100 mL.
 46. An oil-in-water emulsion comprising: a) fish oiltriglycerides consisting of glycerol which is esterified with fattyacids wherein said fatty acids comprise EPA and DHA in an amount of atleast 45% by weight of said fatty acids and the total amount of omega-3fatty acids is at least 60% by weight of said fatty acids, and b) atleast one medium chain triglyceride oil, and wherein the fish oiltriglycerides are present in an amount of at least 51% by weight basedon the total weight of the oil component, and the medium chaintriglycerides are present in an amount of 10% to 49% by weight based onthe total weight of the oil component.
 47. The oil-in-water emulsion ofclaim 46 wherein the fish oil triglycerides are present in an amountranging from 51% to 90% by weight based on the total weight of the oilcomponent.
 48. The oil-in-water emulsion of claim 46 or 47 wherein theoil component additionally comprises a vegetable oil.
 49. Theoil-in-water emulsion of claim 48 wherein the vegetable oil is presentin an amount of up to 10% by weight, preferably from 2% to 8% by weightbased on the total weight of the oil component of the oil-in-wateremulsion.
 50. The oil-in-water emulsion of claim 48 or 49 wherein thevegetable oil is selected from the group consisting of soybean oil andsafflower oil and mixtures thereof.
 51. The oil-in-water emulsion of atleast one of claims 46 to 50 comprising the oil component in an amountranging from 5% to 30% by weight, preferably 15% to 25% by weight, inparticular 20% by weight based on the total weight of the emulsion. 52.The oil-in-water emulsion of at least one of claims 46 to 51additionally comprising at least one phospholipid which is preferablyselected from the group of phospholipids derived from egg or soya. 53.The oil-in-water emulsion of claim 52 wherein the phospholipid is aphosphatidyl choline.
 54. The oil-in-water emulsion of claim 52 or 53wherein the phospholipid is present in a weight ratio of phospholipid totriglycerides ranging from 0.05 to 0.07, preferably 0.06.
 55. Theoil-in-water emulsion of at least one of claims 46 to 54 additionallycomprising an isotonic agent, preferably in a concentration ranging from20 to 25 g/L.
 56. The oil-in-water emulsion of claim 55 comprisingglycerol as isotonic agent.
 57. The oil-in-water emulsion of at leastone of claims 46 to 56 comprising a pH adjusting agent.
 58. Theoil-in-water emulsion of claim 57 comprising sodium oleate as the pHadjusting agent.
 59. The oil-in-water emulsion of claim 57 or 58 whereinthe pH adjusting agent is present in a concentration of up to 3 g/L. 60.The oil-in-water emulsion of at least one of claims 46 to 59 wherein thepH value of the emulsion ranges from 6 to 9, preferably from 6 to 8.5,more preferably 7.5 to 8.5.
 61. The oil-in-water emulsion of at leastone of claims 46 to 60 additionally comprising an antioxidant which ispreferably present in a concentration of up to 1 g/L.
 62. Theoil-in-water emulsion of claim 61 wherein the antioxidant isα-tocopherol.
 63. The oil-in-water emulsion of at least one of claims 46to 62 wherein the emulsion is parenterally applicable.
 64. Oil-in-wateremulsion of at least one of claims 46 to 63 wherein the mean dropletdiameter of the oil droplets is below 250 nm, preferably below 240 nm at20° C.
 65. A pharmaceutical composition comprising or consisting of anoil-in-water emulsion of at least one of claims 46 to
 64. 66.Pharmaceutical composition of claim 64 for use in the prophylaxis ortreatment of the group of diseases consisting of systemic inflammatoryresponse syndrome (SIRS), respiratory distress syndrome (RDS),nutritional and/or dietary cause of liver disease, an iatrogenic causeof liver disease, a pathological cause of liver disease, an immunemodulation, head trauma, post operative surgical stress, a myocardialinfarction and cystic fibrosis.